Preparing the Heart for Attack

14 September 2008

Interview with

Daria Mochly-Rosen, Stanford University

Chris - Now there may be a new way to tackle heart disorders and Daria Mochly-Rosen is a research at Stanford in America. She's come up with a new way perhaps to create a condition called cardiac preconditioning. This is where the heart in some way becomes resistant to the effects of stress and reduced oxygen and blood flow, perhaps because you've had that for a while so if you have preconditioning you're resistant to those effects. She's actually found a way of minimising the damage to hearts if you give animals a certain drug. We're now going to find out whether or not this might work in humans. Hello Daria, thank you for joining us.

Daria - Hello, thank you for having me.

Chris - So tell us a bit about this research.

Human HeartDaria - It started as you told the audience with a quest to understand how the heart is managing to protect itself from damage if a full-blown heart attack occurs. Quite a few researchers were trying to see if we could put it in a bottle, so to speak. First we took a number of agents which give the heart a preconditioning-like effect and see whether something in common came up. What we found is that this enzyme called aldehyde dehydrogenase is the one that changes more consistently with the amount of damage to the heart after heart attack: or a model of heart attacks. The bigger the damage, the lower the activity of the enzyme. The smaller the damage the higher the activity of the enzyme. 

Chris - Is your theory then that what's going on in people who have long-standing heart disease, the heart by being stressed makes more of this enzyme so that if someone then has a heart attack they're more protected. If someone has a heart attack out of the blue they have low levels of this enzyme and therefore the heart is more damaged.

Daria - Actually what's interesting is not that the heart is making more of the enzyme but it actually makes it a little bit more active. We were interested to see how it happens and we found the mechanism but then we thought this is all a correlation that increasing the activity of the enzyme is really correlating with decreased damage.

Chris - How does the enzyme work, Daria?

Daria - It is getting rid of what's called free-radicals. These massive things that accumulate in the organ when there is less oxygen in the atriums. In fact, free-radicals are accumulating in a variety of diseases and this enzyme is one of the important enzymes. It gets rid of those very reactive agents that accumulate in the organ during this ischaemic event, heart attack events.

Chris - How are you managing to increase the levels of your enzyme in the experimental system?

Aldehyde dehydrogenaseDaria - So what we do is we do not increase the level of the enzyme but we increase its activity. We search for a small molecule that can enhance the activity of the enzyme by screening hundreds of thousands of molecules in a sensitive assay. We found this little molecule being more-or-less the size of aspirin that can increase the activity of the enzyme by about two-fold.

Chris - This is in animals, presumably?

Daria - That's absolutely just right. Nothing has been done in animals other than rats. We like to point out that studies in rats, as encouraging as they are, they are not really telling you unequivocally whether it will work in humans. It's yet to be determined.

Chris - Sure but it's a guide isn't it? You would put this molecule into the animal or the human in future. It would in some way increase the activity of their own aldehyde dehydrogenase enzyme . This would protect the heart in the context of a heart attack. How much damage do you think you could prevent with this strategy?

Daria - In the rats when we know exactly. When we looked first we were inducing it we can reduce the damage by 60%. In human as you know we unfortunately don't know when a patient will have a heart attack and how long the heart attack will be and so on and so forth. It's difficult to determine how much protection you will have. We are particularly encouraged with this finding for uses in scenarios other than just heart attacks. For example, during bypass surgery when there is a period that is determined by the surgeon in which the oxygen and nutrients to the heart are reduced. We also think that it will be able to protect the brain, for example, during this period of low flow of blood through the body.

Chris - Thank you very much, Daria

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